The Potential of Gene Therapy in Inherited Retinal Disease
Arun Upadhyay, PhD, the chief scientific officer and head of research, development, and Medical at Ocugen, discussed OCU400, the company’s gene-agnostic gene therapy for IRDs.
Arun Upadhyay, PhD
Substantial unmet need remains for patients with inherited retinal diseases (IRD). Although, because IRDs such as retinitis pigmentosa (RP) can be linked to a wide range of genes, developing traditional targeted gene therapy approaches may not be practical.
Ocugen is seeking to solve this problem with its gene-agnostic approach to gene therapy in IRDs. Notably, one of the company’s gene therapy products based on this platform, OCU400, recently entered a phase 3 clinical trial (liMeliGhT; NCT06388200). CGTLive® spoke with Arun Upadhyay, PhD, the chief scientific officer and head of research, development, and Medical at Ocugen, to learn more.
CGTLive: Can you speak about the current landscape of care for retinal disorders and unmet needs that remain?
Arun Upadhyay, PhD: If you look at the IRD space in general, most of these indications are inherited in nature and they're a genetic disorder. Currently, we have only one product approved for the treatment of patient with mutation in the RP65 gene, which represents only 1% to 2% of the total RP patient population. As such, there is a significant unmet medical need. If you look at retinitis pigmentosa (RP), it affects approximately 1 in 4000 individuals globally and more than 100,000 patients are affected by this condition in the US. It is characterized by, a general night blindness and there's a gradual loss of peripheral vision, which can ultimately lead to blindness. Currently, there is no other treatment available for these patients. If you look at this particular disease landscape, more than 100 genes are associated with this RP condition, and one of the biggest challenges in developing therapy for diseases like this is genetic and clinical heterogeneity. That leads to basically developing an individualized gene therapy based product, which is a daunting, and almost, I can say, an unfeasible task.
Unlike traditional gene therapies that target a specific mutation, our Modifier Gene Therapy approach basically aims to modify the underlying disease pathway affected by various mutations in these RP patients. Our approach is more gene-agnostic in nature, which not only enhances the function of the photoreceptor, but also helps with preserving the surviving retinal cells through cellular and molecular homeostasis.
Can you tell us about OCU400 and its phase 3 trial?
OCU400 is our first candidate right now in a later stage, phase 3 trial. It is based on our Modifier Gene Therapy approach and, as I mentioned, basically it has potential to provide benefits to RP patients with a wide range of gene mutations. In contrast to replacing the defective gene or augmenting the defective gene, our approach is focused on restoring the retinal function through modifying the various cellular and molecular pathways. Currently, we are in a phase 3 study for RP. This study is designed to evaluate the safety and efficacy of OCU400 in RP patients. This study consists of 2 arms, a RHO and gene agnostic arm, and it targets both adult and pediatric populations at the different stages of the disease. We are planning to enroll a total of 150 patients in this study, which will be equally distributed in these 2 arms, a rhodopsin and a gene agnostic arm, and it targets both adult and pediatric populations at the different stages of the disease. We are planning to enroll a total of 150 patients in this study, which will be equally distributed in these 2 arms. In each arm, participants will be randomized into a 2 to 1 ratio to receive either OCU400 as a treatment or remain as an untreated control.
The primary efficacy end point for this particular phase 3 study is assessment of patient mobility through a maze-like path under different light conditions, or in other words, what we call under different lux level conditions. We named this test LDNA, Luminance Dependent Navigation Assessment. Basically what we are doing on this test is that the way we define the treatment benefit is someone who shows improvement of 2 lux levels or more from baseline after 12 months of treatment. How did we come to this number? It is based on our phase 1/2 study, where over 60% of the intent to treat patient population saw a vision improvement of 2 lux levels or more. Based on this phase 1/2 responder outcome, we powered our phase 3 study more than 95%, with the assumption of 50% patient responders in our phase study 3 meeting a 2 lux or more level of improvement as a responder criteria.
This transcript has been edited for clarity.
